It is planned to examine the possible rate limiting reactions in gluconeogenesis and ketogenesis under various physiological states. These various states will be produced by the use of diets and/or hormones. The use of isolated liver cells techniques will be used in conjunction with various substrates or combination of substrates to ascertain which reactions may be rate limiting under each of these conditions. The relationship of gluconeogenesis and ketogenesis will also be examined under these various conditions to see if this relationship, as occurs in starvation and diabetes, is correlated in many other states. The possibility of metabolic compartmentalization, in addition to sub-cellular organelle compartmentalization, in the liver will also be examined. The relationship of enzyme activity and metabolic potential under "optimal" conditions will also be examined in the perfused liver of animals treated with various diets and/or hormones to determine if enzyme activity is limiting in the presence of excess substrate or whether other factors become important in a system as complex as the perfused liver. The role of hormones and their interactions in regards to producing "optimal" conditions are also being considered. A study of arginine metabolism and the urea cycle particularly in regards to the in vivo synthesis of arginine and its role in metabolism such as protein synthesis and urea synthesis. These factors will include effects of diet and hormones on permeability of arginine, ornithine, and citrulline in the liver as well as potential rate of arginine synthesis by the body. The control factors of urea synthesis are also being investigated. BIBLIOGRAPHIC REFERENCES: 1977 Smith, S.B., S. Briggs, K.C. Triebwasser and R.A. Freedland. Re-evaluation of amino-oxyacetate as an inhibitior. Biochem. J. 162:453-455. 1977 Simpson, R.C. and R.A. Freedland. The isolation and identification of 2-methyl-2, 4-thiazolidine dicarboxylate as a by-product in the conversion of cysteine to glucose in the perfused rat liver. Biochimica et Biophysica Acta 496:12-19.